Method for coating a surface of a component

ABSTRACT

The invention relates to a method for coating a surface ( 44 ), in particular a microstructured surface, of a component ( 55 ) comprising different materials, in particular glass and silicon, wherein the surface ( 44 ) is first activated and then coated, wherein an oxidising solution, a basic solution or an acid-oxidising solution is used to activate the surface ( 44 ).

The invention relates to a method for coating a surface, in particular a micro-structured surface, of a component comprising different materials, in particular glass and silicon, wherein the surface is first activated and then coated, a coated component and a nebuliser having a coated component.

WO 91/14468 A1 and WO 97/12687 A1 each show a nebuliser which is marketed in the form of an inhaler under the brand name “Respimat” by Boehringer Ingelheim Pharma GmbH & Co. KG. The nebuliser is used for propellant-free administration of a metered quantity of a liquid medicament for inhalation. In the inhaler, liquid medicament formulations are stored in a reservoir and conveyed through a riser tube into a metering chamber from which they are finally expelled through a nozzle.

The nozzle has a liquid inlet side and a liquid outlet side. On the liquid inlet side is an opening through which the liquid medicament coming from the metering chamber is able to enter the nozzle. On the opposite side, the free end face of the nozzle, the liquid then emerges through two nozzle openings which are aligned such that the jets of liquid emerging from the openings strike one another and are thereby nebulised. The nozzle openings are formed in at least two superimposed plates, at least one of which has a microstructure, so that the two plates firmly attached to one another define on one side a liquid inlet, adjoining which is a channel and/or filter system that opens into the nozzle openings. The two plates with the microstructure and the nozzle openings are referred to as a uniblock in the context of the Respimat technology.

A nebuliser of this kind usually delivers formulations based on water or water/ethanol mixtures and within a short time is able to nebulise a small amount of the liquid medicament formulation, in the therapeutically required dose, into an aerosol suitable for therapeutic inhalation. Using the nebuliser it is possible to nebulise quantities of less than 100 microlitres in, for example, one actuation to form an aerosol with an average particle size of less than 20 microns, such that the inhalable part of the aerosol already corresponds to the therapeutically effective amount.

In the nebuliser with Respimat technology the medicament solution is converted by a high pressure of up to 300 bar into a slowly moving aerosol mist destined for the lungs, which can then be breathed in by the patient. In rare cases, during the use of the nebuliser, residues of the formulation solution may adhere to the nozzle outlets as a contaminant, accumulate thereon and lead to clogging of the nozzle outlets, which may be accompanied by a deflection of the jets of liquid and a change in the fine particle fraction. Even if this effect is very rare in a nebuliser of the Respimat technology, there is a need to avoid deposits for reasons of quality control.

To avoid contamination of an outer surface of the nozzle system or a mouthpiece by precipitated liquid with fine particle fractions, DE 103 00 983 A1 proposes that the corresponding surfaces should be at least partially micro- or nano-structured.

The aim of the invention is to provide a method and a component as well as a nebuliser comprising a component of the kind described hereinbefore which is of self-cleaning design with a thin functionalising coating.

According to the invention the objective is achieved by a method which uses an oxidising solution, a basic solution or an acid-oxidising solution to activate the surface.

Surprisingly, it has been found that the solutions mentioned above can be used to activate surfaces of two different materials, particularly silicon and glass, which are joined together to form a monolithic component. In the literature, a special solution is always assigned to a particular material in order to produce the reactive groups needed for interface functionalisation, as the activation has to be matched to the particular substrate and specifically developed for different materials. For example, the activation of the surface of the component is carried out using a so-called piranha solution, namely the powerfully oxidising peroxomonosulphuric acid (concentrated sulphuric acid: hydrogen peroxide solution (30%) in the ratio 7:3), at 70° C. for 20 minutes. Alternatively, RCA cleaning may be used which is normally used for wafer cleaning in microelectronics. This uses the following solution: water:ammonia solution (25%):hydrogen peroxide solution (30%), in the ratio 5:1:1. The component is exposed to the solution at 75° C. for 20 minutes.

Preferably, a cell cleaner is used as the basic solution for activating the surface. Preferably the cell or glass cleaner made by Hellma GmbH & Co. KG, of Müllheim, Germany, known under the brand name “ Hellmanex solution” is used, as an aqueous 2% solution at 70° C. for 2×20 minutes in the ultrasound bath, although the manufacturer advises against the use of ultrasound in conjunction with their “Hellmanex solution”. The Hellmanex solution ensures activation which is effective on all kinds of materials, particularly silicon and glass, in order to produce reactive interfaces.

Expediently, before being activated, the surface is cleaned, particularly with isopropanol and water. The component is immersed in isopropanol for five minutes and in water for five minutes. According to one feature, the surface is treated in a solution of hydrofluoric acid after cleaning. It is bathed for about 20 minutes in an aqueous 3% hydrofluoric acid solution (HF).

According to a further feature, functional silanes in non-polar, aprotic or polar-protic solvents are used to coat the surface. The coating is very thin and is provided as a monolayer. The component with its activated surfaces is immersed for about two hours, in a toluene reaction, in a 0.1 to 1% solution of functional trichlorosilanes or dimethylmonochlorosilanes in dry non-polar, aprotic solvents such as toluene, benzene, carbon tetrachloride, n-alkanes (C₅-C₁₀) or the like. Then the component is dried in a nitrogen current and heat-treated in an oven for about one hour at about 120° C. After the heat-treatment excess and non-covalently bound residues are washed off the component using toluene and isopropanol. When the reaction is alcoholic, particularly isopropanolic, first of all a reaction solution has to be activated in order to be able to carry out interface functionalisation of the component with its activated surfaces of silicon and glass. A 0.1 to 1% solution of functional triethoxysilanes in 2-propanol/water/hydrochloric acid (HCl) in a ratio of 90 to 98:2 to 10:0.2 to 0.5 is stirred for about five hours at ambient temperature. Then the component with its activated surfaces is immersed in the solution for about two hours. After the component has been taken out of the solution the excess solution is carefully removed from the component, for example by allowing it to drip onto an absorbent non-woven fabric. Then the component is kept at a controlled 120° C. for about two hours. Any excess and non-covalently bound residues are washed off the component using isopropanol and water after the heat treatment. The following categories of materials are used to coat the surfaces: perfluoroalkylsilanes, alkylsilanes, aminoalkylsilanes, carboxylic acid silanes, trimethylammonium silanes of different chain lengths, particularly C₄-C₁₈, while the functional silanes used may be reactive trihalosilanes (R₁—Si—R₃, where R═Cl, Br), monohalodimethylsilanes (R₁—Si(CH3)₂R, where R═Cl, Br) or trialkoxysilanes (R₁—Si—R₃, where R═methoxy or ethoxy groups).

To ensure satisfactory wetting of the surfaces of the component that are to be coated, in order to coat the surfaces the component is advantageously treated with ultrasound in the reaction solution. The ultrasound treatment in particular ensures the exchange of the reaction solution in the capillaries of the component.

The objective is achieved in the component comprising at least two plates firmly joined together, at least one of which has a microstructure to form a channel and/or filter system and at least one nozzle opening adjoining it, by the fact that at least the surface of the microstructure has a coating which has been applied by the method described above.

As a result of this, any interaction of components and particles of the formulation expelled through the nozzle opening with the interfaces of the component is prevented. The free energy of the surface and hence its wettability is minimised in this area, resulting in a reduction in the immobilisation of residues of material on the nozzle outlet, i.e. in the immediate vicinity of the nozzle opening. When the component is used, the residues of material are expelled from the component and the coated component is self-cleaning, thanks to the use of the monomolecular, covalently bound non-stick coating. The functionalisation can be altered variably, depending on the interaction of different ingredients of the formulation with the interfaces of the component and may, for example, have hydrophilic or hydrophobic, positively or negatively charged, oleophillic or oleophobic properties.

One plate expediently consists of silicon while the other plate is glass. The silicon plate is provided with a microstructure, i.e. it comprises the channel or filter system and the nozzle openings and is adhesively bonded to the plate made of glass.

The component consists of the two plates of glass and silicon firmly joined together, while the plate consisting of silicon has one or more microstructured channels which connect the inlet side to the outlet side. On the outlet side there may be at least one round or non-round nozzle opening 2-10 μm deep and 5-15 μm wide, the depth preferably being 4.5 to 6.5 μm and the length being 7 to 9 μm. In the case of a plurality of nozzle openings, preferably two, the directions of flow through the nozzles in the component which essentially forms a nozzle body extend parallel to one another or are inclined towards one another in the direction of the nozzle opening. In a component having at least two nozzle openings on the outlet side, the directions of flow may slope towards one another at an angle of 20° to 160°, preferably at 60° to 150°, more preferably 70° to 100°. The nozzle openings are preferably arranged at a distance of 10 to 200 μm, more preferably at a distance of 10 to 100 μm, particularly preferably 30 to 70 μm. A distance of 50 μm is most preferred. The directions of flow meet accordingly in the vicinity of the nozzle openings. In the interests of simplicity an embodiment will be described hereinafter in which only the silicon plate of the component has relief-like microstructures, but not the plate made of glass. In other embodiments the situation is exactly the reverse, or both plates comprise these microstructures. On the silicon plate, a set of channels may be formed on the flat surface in order to create a plurality of filter passages (filter channels) in co-operation with the substantially flat surface of the glass plate. Additionally, the silicon plate may have a plenum chamber the ceiling of which is in turn formed by the glass plate. The plenum chamber may be provided in front of or behind the filter channels. It is also possible to have two such plenum chambers. Another set of channels on the substantially flat surface of the silicon plate which is provided after the filter channels forms, together with the glass plate, a set of channels that provide a plurality of nozzle outlet passages. Preferably, the total cross-sectional area of the nozzle outlets is 25 to 500 μm². The entire cross-sectional area is preferably 30 to 200 μm². In another embodiment this nozzle construction also has only a single nozzle opening. In other embodiments of this kind the filter channels and/or the plenum chamber are omitted. Preferably, the filter channels are formed by projections arranged in a zig-zag configuration. Thus, for example, at least two rows of the projections form a zig-zag configuration of this kind. A number of rows of projections may also be formed, the projections being laterally offset from one another in order to form additional rows that are skewed in relation to these rows, these additional rows mentioned above then forming the zig-zag configuration. In such embodiments the inlet and outlet may each comprise a longitudinal slot for unfiltered or filtered fluid, each of the slots being substantially the same width as the filter and substantially the same height as the projections on the inlet and outlet sides of the filter. The cross-section of the passages formed by the projections may be perpendicular to the direction of flow of the fluid and may decrease from one row to the next, viewed in the direction of flow. Also, the projections that are arranged closer to the inlet side of the filter may be larger than the projections that are arranged closer to the outlet side of the filter. In addition, the spacing between the silicon plate and the glass plate may become narrower in the region from the inlet side to the outlet side. The zig-zag configuration which is formed by at least two rows of projections has an angle of inclination of preferably 20° to 250°. Further details of this construction of the component can be found in WO 94/07607.

Finally, the objective is achieved with a nebuliser for delivering a specific amount of a fluid, in particular a fluid containing a medicament, as an aerosol, using the component of the kind described hereinbefore.

It will be understood that the features mentioned above and those to be explained hereinafter may be used not only in the particular combinations stated but also in other combinations. The scope of the invention is defined only by the claims.

The invention is hereinafter described in more detail by means of an embodiment by way of example, by reference to the attached drawings, wherein:

FIG. 1 is a longitudinal section through a nebuliser according to the invention with a tensioned spring,

FIG. 2 is a longitudinal section through the nebuliser according to FIG. 1 with the spring relaxed,

FIG. 3 is a perspective view of a component according to the invention,

FIG. 4 is a front view of the component according to FIG. 3 and

FIG. 5 is a magnified partial representation of the component according to FIG. 3.

An upper housing part 51 of the nebuliser comprises a pump housing 52 on the end of which is mounted a holder 53 for a nebuliser nozzle. In the holder 53 is a recess 54 that widens outs and the component 55 in the form of a nozzle body. A hollow piston fixed in a power take-off flange 56 of a locking clamping mechanism projects partly into a cylinder of the pump housing 52. At its end the hollow piston 57 carries a valve body 58. The hollow piston 57 is sealed off by a gasket 59. Inside the upper housing part 51 is a stop 60 of the power take-off flange 56 on which a compression spring 68 rests. After the tensioning of the compression spring 68 a locking member 62 slides between a stop 61 on the power take-off flange 56 and a support 63 in the upper housing part 51. An actuating button 64 is connected to the locking member 62. The upper housing part 51 ends in a mouthpiece 65 and is closed off by a removable protective cap 66.

A spring housing 67 with the compression spring 68 is rotatably mounted on the upper housing part 51 by means of snap-fit lugs 69 and a rotary bearing. A lower housing part 70 is pushed over the spring housing 67 and inside the spring housing 67 is a storage container 71 for fluid 72 which is to be nebulised. The storage container 71 is closed off by a stopper 73 through which the hollow piston 57 projects into the storage container 71 and dips its end into the fluid 72, i.e. the supply of active substance solution.

A spindle 74 for a mechanical counter (optional) is provided in an outer surface of the spring housing 67. A drive pinion 75 is located at the end of the spindle 74 facing the upper housing part 51. On the spindle 74 is a slider 76.

The component 55—a so-called uniblock—comprises two plates 40, 41 firmly joined together, of which one plate 40 is made of silicon and has a microstructure 42 for forming a channel or filter system and an adjacent nozzle opening 43. The silicon plate 40 is firmly attached to the glass plate 41 on the side having the microstructure 42.

At least the surface 44 of the microstructure 42 has a coating consisting of functional silanes which prevents any interaction of ingredients and particles of the formulation expelled through the nozzle opening 43 with the interfaces of the component 55. During the use of the nebuliser comprising the component 55, the material residues are expelled from the component 55 and the coated component 55 is self-cleaning thanks to the use of the monomolecular, covalently bound non-stick coating.

The surfaces 44 of the component 55, particularly the microstructure 42, are first cleaned by dipping the component 5 first into isopropanol for five minutes and then into water for five minutes. Then the component 55 is bathed for about 20 minutes in an aqueous 3% hydrofluoric acid solution (HF).

The activation of the surface 44 itself is carried out using a cell cleaner, particularly the cell or glass cleaner known by the brand name “Hellmanex solution” and produced by Hellma GmbH & Co. KG, of Müllheim, Germany, as an aqueous 2% solution, at 70° C. for 2×20 minutes in an ultrasound bath.

For functionalisation, 1H,1H,2H,2H-perfluorooctyltriethoxysilane is used, for example, which is marketed for example under the brand name Dynasylan by Evonik AG of Düsseldorf. After the component 55 has been exposed for about two hours to a solution containing the functional silane under the effect of ultrasound, the excess solution is allowed to drip off the component 55 and the component is treated for about one to two hours at 120° C. in an oven. After the heat treatment any excess and non-covalently bound residues are washed off the component 55 using isopropanol and water. 

1. A method for coating a microstructured surface (44) of a component (55) comprising glass and silicon, wherein the surface (44) is first activated and then coated, characterised in that an oxidising solution, a basic solution or an acid-oxidising solution is used to activate the surface (44).
 2. The method according to claim 1, characterised in that a cell cleaner is used as the basic solution for activating the surface (44).
 3. The method according to claim 1, characterised in that before the activation the surface (44) is cleaned using isopropanol and water.
 4. The method according to claim 3, characterised in that after cleaning the surface (44) is treated in a solution of hydrofluoric acid.
 5. The method according to claim 1, characterised in that for coating the surface (44), functional silanes in non-polar, aprotic or polar, protic solvents are used.
 6. The method according to claim 1, characterised in that for coating the surface (44) the component (55) is treated with ultrasound in the reaction solution.
 7. The method according to claim 1, characterised in that after coating the component (55) is dried and heat-treated.
 8. The method according to claim 1, characterised in that the coated component (55) is washed.
 9. A component which comprises at least two plates (40, 41) firmly joined to one another, of which at least one plate (40) has a microstructure (42) for forming a channel and/or filter system and at least one nozzle opening (43) adjacent thereto, while at least the surface (44) of the microstructure (42) has a coating which is applied by the method of claim
 1. 10. The component according to claim 9, characterised in that one plate (40) consists of silicon and the other plate (41) consists of glass.
 11. A nebuliser for delivering a specific amount of a fluid (72) comprising a medicament, as an aerosol using a component (55) according to claim
 9. 12. The nebuliser according to claim 11, characterised by a lower housing part and an upper housing part mounted to be rotatable against each other, wherein in the upper housing part (51) is formed a spring housing (67) having a compression spring (68) which is tensioned by rotating the two housing parts using a locking clamping mechanism, preferably in the form of a screw thread or gear, and is relaxed by pressing an actuating button on the upper housing part (51), the compression spring (68) moving a power take-off flange (56) which is connected to a hollow piston (57) on the lower end of which a container can be fitted and at the upper end of which are located a valve and a metering chamber which is connected in a fluid-carrying relationship with the component (55) embodied as a nozzle system, said component (55) being arranged in the upwardly open region of the upper housing part (51). 